Guidelines for the management

of dyslipidaemia in patients with

diabetes mellitus
Quick reference guide
More than 60% of type 2 diabetic subjects in the Eastern Mediterranean Region have
some degree of dyslipidaemia. More than 40% of type 2 diabetic individuals have
hypercholesterolemia and a further 23% have hypertriglyceridaemia and/or a low level
of HDL cholesterol. In contrast, <25% of non-diabetic subjects are hyperlipidaemic.
In addition to being the most common lipid abnormality in type 2 diabetes mellitus,
hypertriglyceridaemia is also a feature of impaired glucose tolerance and impaired
fasting glucose. The purpose of this quick reference guide is to offer proper information
and guidance to primary health care physicians, specialists and consultants, and also to
policy-makers. They do not attempt to make rigid clinical decisions for physicians and
patients. Each clinician must decide, with their patients, the best approach for managing
dyslipidaemia in diabetes.
Characteristics of diabetic dyslipidaemia
Diabetic dyslipidaemia is characterized by:
elevated triglycerides
low high density lipoprotein (HDL) cholesterol
shift in low-density lipoprotein (LDL) particle density towards small, dense LDL (type B)
tendency towards postprandial lipaemia.
Triglycerides are considered to have atherogenic properties.
HDL is considered a protective lipoprotein because it contributes to reverse cholesterol
transport.
Small, dense LDL is considered more atherogenic than large, buoyant LDL because it is more
prone to oxidation and can trigger inflammatory processes.
Classification
The following tables classify the levels of total, LDL and HDL cholesterol and triglycerides.
LDL cholesterol classification
LDL cholesterol (mmol/L) LDL cholesterol (mg/dL) Classification
<2.58 <100 Optimal
2.583.33 100129 Near or above optimal
3.364.11 130159 Borderline high
4.134.88 160189 High
4.91 190 Very high
Total cholesterol classification
Total cholesterol (mmol/L) Total cholesterol (mg/dl) Classification
<5.17 <200 Desirable
5.176.18 200239 Borderline high
6.20 240 High
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HDL cholesterol classification
HDL cholesterol (mmol/L) HDL cholesterol (mg/dL) Classification
<1.03 <40 Low
1.55 60 High
Triglycerides classification
Triglycerides (mmol/L) Triglycerides (mg/dL) Classification
<1.69 <150 Optimal
1.692.25 150199 Borderline high
2.265.63 200499 High
5.64 500 Very high
Screening
A fasting lipid profile is recommended on a yearly basis for patients with diabetes. The
frequency may be decreased to every other year for patients with optimal lipid levels.
A lipid profile should include measurement of total cholesterol, HDL cholesterol and
triglycerides. LDL cholesterol can be calculated, as long as triglycerides are below 400
mg/dL, using the formula LDL cholesterol = total cholesterol HDL cholesterol [1/5 x
triglycerides]. Otherwise serum LDL cholesterol may need to be measured directly.
Screening is important in order to identify patients with suboptimal lipid profiles and then
institute corrective measures for either primary or secondary prevention.
If elevated LDL cholesterol or triglycerides are found, clinical and laboratory assessment
should be performed in order to rule out secondary causes of dyslipidaemia, such as:
hypothyroidism (symptoms, check thyroid-stimulating hormone)
obstructive liver disease (liver function tests)
chronic renal disease (renal function tests, creatinine clearance, urinalysis)
drugs (estrogen, progestins, corticosteroids, thiazides)
alcohol (raises triglycerides).
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Management goals of diabetic dyslipidaemia
The primary target of therapy is LDL cholesterol, unless serum triglycerides are 500 mg/dL
in which case triglyceride-lowering therapy should be started immediately because of the
high risk of pancreatitis.
If or when triglycerides levels are <500 mg/dL, the primary target of treatment is LDL
cholesterol and the goal LDL for patients with coronary heart disease or coronary heart
disease equivalent (including diabetes) is an LDL cholesterol <100 mg/dL.
When this is achieved, attention is then shifts to triglycerides. If triglycerides are 200 mg/
dL, the sum of LDL plus very low density lipid (VLDL) cholesterol, also referred to as non-
HDL cholesterol, becomes the secondary target since VLDL, and especially its remnants, are
considered atherogenic.
Non-HDL cholesterol is equal to [total cholesterol HDL cholesterol], and its goal is 30 mg/dL
above the LDL cholesterol goal, i.e. non-HDL goal should be <130 mg/dL in patients with
diabetes, assuming a normal VLDL cholesterol to be 30 mg/dL.
For patients with low HDL cholesterol (<40 mg/dL), consider interventions to raise HDL
cholesterol level but only after the goals for LDL cholesterol and non-HDL cholesterol (for
patients with triglycerides 200 mg/dL) have been achieved.
Management of dyslipidaemia
2
4
There is no goal specified for raising HDL in patients with isolated low HDL cholesterol.
However, even minimal elevation of HDL should translate into improvement in cardiovascular
risk.
Lipid profiles should be repeated for confirmation when in doubt. The following protocol
summarizes the approach for managing dyslipidaemia.
It is recommended to start statin therapy in patients with LDL cholesterol 100 mg/dL if
they have a history of coronary heart disease.
Healthy lifestyle changes
Dietary interventions, the cornerstone of diabetes management, are also an important means
of controlling dyslipidaemia in both diabetic and non-diabetic individuals. Considerable
evidence demonstrates the beneficial changes in diabetic dyslipidaemia following dietary
alterations, such as changes in nutrient composition.
Exercise is as an important method of improving diabetes control and reducing the risk
of cardiovascular disease. Additional evidence suggests that it has beneficial effects on
dyslipidaemia, such as significantly increasing HDL cholesterol levels.
Healthy lifestyle practices should therefore be emphasized in patients with diabetes. They
include:
increased physical activity
weight reduction for obese patients
reduction of food items high in cholesterol, saturated fats and trans-fatty acids
increased intake of viscous (soluble) fibres and of plant stanols and sterols which help
lower serum cholesterol by limiting its absorption from the gut.
Composition of a healthy diet for patients with diabetes
Nutrient Recommended intake
Saturated fat + trans-fatty acid Less than 7% of total calories
Polyunsaturated fat Up to 10% of total calories
Monounsaturated fat Up to 20% of total calories
Total fat 30%35% of total calories
Carbohydrate 45%55% of total calories
Protein 15%20% of total calories
Cholesterol Less than 200 mg/day
Fibre 2030 g/day
Total calories (energy) To be determined according to individual needs
(whether to maintain or lose weight)

In patients with elevated triglycerides and low HDL, increasing the intake of unsaturated fat
and decreasing carbohydrates may help correct the lipid abnormalities.
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Drug therapy for diabetic dyslipidaemia
Most patients with diabetes and dyslipidaemia will require drug therapy in order to reach
their goals. Different classes of medications are available, with variable effects on LDL, HDL
and triglycerides.
The following is an outline of the characteristics of the commonly used drug classes.
Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins)
Statins are currently considered the drugs of choice for treatment of high LDL cholesterol.
Some statins, especially the more potent ones, can also lead to significant lowering of
triglycerides. They:
reduce LDL cholesterol by 18%55%
reduce triglycerides by 7%30%
raise HDL cholesterol by 5%15%.
Major side-effects:
myopathy or rhabdomyolysis (rare)
increase in liver enzymes (usually reversible).
Contraindications:
absolute: liver disease
relative: use with certain drugs, due to potential for interaction and increased risk of
myopathy.
Protocol for lipid management
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Statin Dose range
lovastatin 2080 mg
pravastatin 2040 mg
simvastatin 2080 mg
fluvastatin 2080 mg
atorvastatin 1080 mg
rosuvastatin 540 mg
The demonstrated therapeutic benefits of statins are that they:
reduce major coronary events
reduce CHD mortality
reduce coronary procedures (bypass surgery, percutaneous transluminal coronary
angioplasty)
reduce stroke
reduce total mortality.
Bile acid sequestrants
Bile acid sequestrants are considered second line of therapy for high LDL cholesterol, usually
taken in combination with statins.
They can be used as first-line therapy in patients who are allergic or intolerant of statins.
Major actions:
reduce LDL cholesterol by 15%30%
raise HDL cholesterol by 3%5%
may increase triglycerides.
Side-effects:
gastrointestinal distress/constipation
decreased absorption of other drugs when taken concomitantly.
Contraindications:
dysbetalipoproteinemia
raised triglycerides (especially >400 mg/dL).
Drug Dose range
cholestyramine 416 g
colestipol 520 g
colesevelam 2.63.8 g
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Demonstrated therapeutic benefits:
reduce major coronary events
reduce CHD mortality.
Cholesterol absorption inhibitor
This is a new class of cholesterol lowering medication, aimed at lowering LDL cholesterol.
The compound in this class is typically used in combination with a statin when further LDL
lowering is desired.
Major actions:
reduce LDL cholesterol by 15%20%
raise HDL cholesterol by 3%4%
no effect on triglycerides.
Side-effects:
minimal
Drug Dose
Ezetimibe 10 mg
Nicotinic acid
Despite its side-effects, nicotinic acid may be a useful agent in managing diabetic
dyslipidaemia.
It can lead to significant improvement in triglyceride and HDL cholesterol levels, the two
most common abnormalities in patients with diabetes.
Nicotinic acid may lead to a mild increase in blood glucose. However, this hyperglycaemic
effect may be reduced if the drug dosage is kept below 2 g/day.
A mild increase in HbA
1c
is to be expected at dosages of over 1500 mg. Such an increase
may be remedied by adjusting diabetes therapy.
Major actions:
lowers LDL cholesterol by 5%25%
lowers triglycerides by 20%50%
raises HDL cholesterol by 15%35%.
Side-effects:
flushing
hyperglycaemia
hyperuricaemia
upper gastrointestinal distress
hepatotoxicity.
Contraindications:
liver disease
severe gout
peptic ulcer disease.
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Drug form Dose range
Immediate release (crystalline) 1.53 g
Extended release 12 g
Demonstrated therapeutic benefits:
reduces major coronary events
possible reduction in total mortality.
Fibric acids
Fibrates are considered first line therapy for patients with high triglycerides (and adequate
LDL).
The newest agent, fenofibrate, appears to have a lower potential for drugdrug
interaction.
Major actions:
lower LDL cholesterol by 5%20% (with normal triglycerides)
may raise LDL cholesterol (with high triglycerides)
lower triglycerides by 20%50%
raise HDL cholesterol by 10%20%.
Side-effects:
dyspepsia
gallstones
myopathy (especially in patients with renal impairment).
Contraindications:
significant renal or hepatic disease.
Drug Dose
clofibrate 1000 mg, twice daily
gemfibrozil 600 mg, twice daily
fenofibrate 160 mg, once daily
Demonstrated therapeutic benefits:
reduce progression of coronary lesions
reduce major coronary events
Omega-3 fatty acids (fish oils)
The major role of fish oil is in management of high triglycerides, usually as second- or third-
line therapy.
Form Dose
Fish oil 13 g daily
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Combination therapy
A large number of patients with diabetes and dyslipidaemia will require combination therapy
in order to achieve their goals.
Such a situation may occur because one drug is not enough to reach a desirable level for a
particular lipoprotein, or because they have a combination of elevated LDL cholesterol and
elevated triglycerides, thus requiring dual therapy.
Commonly used combinations of lipid-lowering agents
Combination Used for Risk
Statin + bile acid-binding resin High LDL Resin may raise triglycerides
Statin + ezetimibe High LDL No increased risk
Statin + fibrate High LDL + high TG Risk of myositis
Statin + nicotinic acid High LDL + high TG
or High LDL + low HDL Risk of myositis
Fibrate + nicotinic acid High TG
or High TG + low HDL Risk of myositis (low)
TG: triglycerides
Glycaemic control and dyslipidaemia
Improvement in glycaemic control can lead to a less atherogenic lipid profile. Elevated
triglycerides tend to improve consistently when glucose levels are lowered, however, the
effect of better glucose values tends to be more variable with regard to HDL cholesterol and
LDL cholesterol levels.
Insulin has a consistent effect in lowering triglycerides in poorly controlled patients, while
its effects on other lipids tend to be variable. In addition, better glycaemic control is likely
to reduce the amount of glycated LDL, and therefore, reduce LDL atherogenicity.
Always look for secondary causes of dyslipidaemia and treat accordingly.
Reinforcing a healthy lifestyle (adequate diet, weight loss, exercise) is recommended as a
first step for management of dyslipidaemia.
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Further reading
1. Grundy SM et al. AHA conference proceedings prevention conference VI: diabetes and
cardiovascular disease executive summary. Circulation, 2002, 105:22312239.
2. Kreisberg RA, Oberman A. Medical management of hyperlipidemia/dyslipidemia. Journal of
Clinical Endocrinology and Metabolism, 2003, 88:24452461.
3. Haffner SM. Management of dyslipidemia in adults with diabetes. Diabetes Care, 1998,
21:160178.
4. van Dam M, van Wissen S, Kastelein JJP. Declaring war on undertreatment: rationale for
an aggressive approach to lowering cholesterol. Journal of Cardiovascular Risk, 2002,
9:8995.
5. Diabetes Atherosclerosis Intervention Study Investigators. Effect of fenofibrate on progression
of coronary artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention
Study, a randomized study. Lancet, 2001, 357:905910.
6. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol
lowering with simvastatin in 20536 high risk individuals: a randomized placebo-controlled
trial. Lancet, 2002, 360:722.
7. Haffner SM et al. Mortality from coronary heart disease in subjects with type 2 diabetes and
in non-diabetic subjects with and without prior myocardial infarction. New England Journal
of Medicine,1998, 339:229234.
8. Lebovitz HE. Rationale for and role of thiazoliddinedione in type 2 diabetes mellitus. American
Journal of Cardiology, 2002, 90 (Suppl.):34G41G.
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For further information on diabetes mellitus, consult Khatib OMN (ed.) Guidelines for
the prevention, management and care of diabetes mellitus, Cairo, World Health Organization
Regional Office for the Eastern Mediterranean, 2006 (EMRO Technical Publications Series No. 32)
on which this card is based, or contact:
Further information
Noncommunicable Diseases Unit
WHO Regional Office for the Eastern Mediterranean
PO Box 7608, Nasr City
Cairo 11371, Egypt
Email: NCD@emro.who.int; Website: http://www.emro.who.int/ncd/
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